In the present specification, reference is made to the following publications cited for illustrating prior art techniques, in particular conventional MRS imaging, and conventional implementations of certain procedural measures or partial aspects of excitation and encoding sequences.    [1] R. V. Mulkern, L. P. Panych. Echo planar spectroscopic imaging. Concepts Magn. Reson. 13: 213-237 (2001).    [2] T. R. Brown, B. M. Kincaid, K. Ugurbil. NMR chemical shift imaging in three dimensions. Proc. Natl. Acad. Sci. USA 79: 3523-3526 (1982).    [3] A. A. Maudsley, S. K. Hilal, W: H. Perman, H. E. Simon. Spatially resolved high resolution spectroscopy by “four-dimensional” NMR. J. Magn. Reson. 51: 147-152 (1983).    [4] P. Mansfield. Spatial mapping of the chemical shift in NMR. J. Phys. D: Appl. Phys. 16: L235-L238 (1983).    [5] P. Mansfield. Spatial mapping of the chemical shift in NMR. Magn. Reson. Med. 1: 370-386 (1984).    [6] D. N. Guilfoyle, A. Blamire, B. Chapman, R. J. Ordidge, P. Mansfield. PEEP—a rapid chemical-shift imaging method. Magn. Reson. Med. 10: 282-287 (1989).    [7] S. Matsui, K. Sekihara, T. Onodera, H. Shiono. NMR chemical shift imaging method. U.S. Pat. No. 4,689,568 (1985).    [8] S. Matsui, K. Sekihara, H. Kohno. High-speed spatially resolved high-resolution NMR spectroscopy. J. Am. Chem. Soc. 107: 2817-2818 (1985).    [9] S. Matsui, K. Sekihara, H. Kohno. Spatially resolved NMR spectroscopy using phase-modulated spin-echo trains. J. Magn. Reson. 67: 476-490 (1986).    [10] M. Doyle, P. Mansfield. Chemical-shift imaging: A hybrid approach. Magn. Reson. Med. 5: 255-261 (1987).    [11] R. Bowtell, M. G. Cawley, P. Mansfield, A. D. H. Clague. Proton chemical-shift mapping using PREP. J. Magn. Reson. 82: 634-639 (1989).    [12] K. Oshio, W. Kyriakos, R. V. Mulkern. Line scan echo planar spectroscopic imaging. Magn. Reson. Med. 44: 521-524 (2000).    [13] E. Adalsteinsson, P. Irarrazabal, D. M. Spielman, A. Macovski. Three-dimensional spectroscopic imaging with time-varying gradients. Magn. Reson. Med. 33: 461-466 (1995).    [14] P. Webb, D. Spielman, A. Macovski. A fast spectroscopic imaging method using a blipped phase encode gradient. Magn. Reson. Med. 12: 306-315 (1989).    [15] A. Ebel, N. Schuff. Accelerated 3D echo-planar spectroscopic imaging at 4 Tesla using modified blipped phase-encoding. Magn. Reson. Med. 58: 1061-1066 (2007).    [16] P. A. Bottomley. Selective volume method for performing localized NMR spectroscopy. U.S. Pat. No. 4,480,228 (1984).    [17] J. Frahm, K. D. Merboldt, W. Hanicke. Localized proton spectroscopy using stimulated echoes. J. Magn. Reson. 72: 502-508 (1987).    [18] S. Posse, D. Le Bihan. Method and system for multidimensional localization and for rapid magnetic resonance spectroscopic imaging. U.S. Pat. No. 5,709,208 (1998).    [19] S. Posse, C. DeCarli, D. Le Bihan. Three-dimensional echo-planar MR spectroscopic imaging at short echo times in the human brain. Radiology 192: 733-738 (1994).    [20] S. Posse, G. Tedeschi, R. Risinger, R. Ogg, D. Le Bihan. High speed 1H spectroscopic imaging in human brain by echo planar spatial-spectral encoding. Magn. Reson. Med. 33: 34-40 (1995).    [21] S. Matsui, K. Sekihara, H. Kohno. High-speed spatially resolved NMR spectroscopy using phase-modulated spin-echo trains. Expansion of the spectral bandwidth by combined used of delayed spin-echo trains. J. Magn. Reson. 64: 167-171 (1985).    [22] R. Otazo, B. Mueller, K. Ugurbil, L. Wald, S. Posse. Signal-to-noise ratio and spectral linewidth improvements between 1.5 and 7 Tesla in proton echo-planar spectroscopic imaging. Magn. Reson. Med. 56: 1200-1210 (1996).    [23] D. N. Guilfoyle, P. Mansfield. Chemical-shift imaging. Magn. Reson. Med. 2: 479-489 (1985).    [24] US 2009/0091322 A1.    [25] S. Posse, R. Otazo, S. Y. Tsai, A. E. Yoshimoto, F. H. Lin. Single-shot magnetic resonance spectroscopic imaging with partial parallel imaging. Magn. Reson. Med. 61: 541-547 (2009).    [26] K. P. Pruessmann, M. Weiger, M. B. Scheidegger, P. Boesiger. SENSE: Sensitivity encoding for fast MRI. Magn. Reson. Med. 42: 952-962 (1999).    [27] M. A. Griswold, P. M. Jakob, R. M. Heidemann, M. Nittka, V. Jellus, J. Wang, B. Kiefer, A. Haase. Generalized auto-calibrating partially parallel acquisitions (GRAPPA). Magn. Reson. Med. 47: 1202-1210 (2002).    [28] M. A. Brown. Time-domain combination of MR spectroscopy data acquired using phased-array coils. Magn. Reson. Med. 52: 1207-1213 (2004).    [29] S. Hetzer, T. Mildner, H. E. Möller. A modified EPI sequence for high-resolution imaging at ultra-short echo times. Proc. ISMRM 17: 2663 (2009).    [30] PCT/EP 2009/002345 (not published on the priority date of the present specification).    [31] A. Haase, J. Frahm, W. Haenicke, D. Matthei. 1H NMR chemical shift selective (CHESS) imaging. Phys. Med. Biol. 30: 341-344 (1985).    [32] J. P. Felmlee, R. L. Ehman. Spatial presaturation: A method for suppressing flow artifacts and improving depiction of vascular anatomy in MR imaging. Radiology 164: 559-564 (1987).    [33] R. R. Ernst, G. Bodenhausen, A. Wokaun. Principles of Nuclear Magnetic Resonance in One and Two Dimensions. Clarendon Press, Oxford (1987).    [34] F. Schmitt, P. A. Wielopolski. Echo-planar image reconstruction. In: F. Schmitt, M. K. Stehling, R. Turner, eds. Echo-Planar Imaging: Theory, Technique and Application. Springer, Berlin (1998); pp. 141-178.    [35] D. C. Noll, C. H. Meyer, J. M. Pauly, D. G. Nishimura, A. Macovski. A homogeneity correction method for magnetic resonance imaging with time-varying gradients. IEEE Trans. Med. Imaging 10: 629-637 (1991).    [36] L. C. Man, J. M. Pauly, A. Macovski. Multifrequency interpolation for fast off-resonance correction. Magn. Reson. Med. 37: 785-792 (1997).    [37] G. Bodenhausen, R. Freeman, D. L. Turner. Suppression of artifacts in two-dimensional J spectroscopy. J. Magn. Reson. 27: 511-514 (1977).    [38] J. Hennig. The application of phase rotation for localized in vivo proton spectroscopy with short echo times. J. Magn. Reson. 96: 40-59 (1992).    [39] S. W. Provencher. Estimation of metabolite concentrations from localized in vivo proton spectra. Magn. Reson. Med. 30: 672-679 (1993).    [40] M. A. Bernstein, K. F. King, X. J. Zhou. Handbook of MRI Pulse Sequences. Elsevier Academic Press, Amsterdam (2004).
Mapping of the nuclear magnetic resonance (NMR) chemical shift (i.e. spectroscopic information) is of great potential value, for example, for non-invasively studying metabolic heterogeneity of biological tissues in vivo or for investigating the three-dimensional (3D) composition of materials. In such applications, the spectroscopic information introduces a separate dimension besides the three spatial dimensions [1]. Consequently, additional scan time will be required in comparison to standard magnetic resonance imaging (MRI) methods relying on the assumption that only a single resonance from a high-concentration substance, such as the ubiquitous water in biological systems, is present. In conventional chemical shift imaging (CSI) [2, 3], pure phase encoding is used to acquire spectra from different volume elements (voxels) throughout the object. In particular, the spatial encoding step (i.e. application of a magnetic field gradient for spin-warp-type phase encoding) precedes the spectroscopic readout, during which no gradients are applied. This requires that the number of separately encoded measurements equals the number of voxels. For example, assuming a repetition time, TR, of 1 s and a single average, the time needed to encode a two-dimensional (2D), 32×32 spatial matrix for CSI would be 17:04 min!
With echo-planar spectroscopic imaging (EPSI) introduced by Mansfield [4, 5], spatial encoding is employed—at least in one dimension—during acquisition of the spectroscopic dimension, which allows for a much faster acquisition. This is possible, because the acquisition of spectroscopic information in the time domain (i.e. the collection of a free induction decay or an echo signal) is a relatively slow process with a typical sampling interval (spectral dwell time, τω) on the order of 1 ms.
For example, the major brain metabolites in an in vivo proton (1H) spectrum have resonances, which fall between the resonances of fat at 0.9 ppm (terminal methyl groups) and water at 4.7 ppm. This corresponds to a minimal spectral bandwidth, Δν, of 244 Hz (τω=4.1 ms) at a magnetic field strength, B0, of 1.5 T or 468 Hz (τω=2.1 ms) at approximately 3 T. As another example, the chemical-shift range of metabolites routinely observed in in vivo phosphorus (31P) spectra is defined by the signals of phosphomonoesters at 6.6 ppm and of the β-phosphate group of adenosine triphosphate (ATP) at −16.3 ppm, which corresponds to Δν=589 Hz and 1138 Hz (τω=1.7 and 0.9 ms) at 1.5 and approximately 3 T, respectively. Due to sensitivity constraints, a nominal voxel size on the order of 1 cm or more (instead of 1 mm or less as achieved in high-resolution MRI) is sufficient in typical spectroscopic-imaging applications. For integrating spatial encoding during the intervals defined by τω, gradient slew-rate performance is of paramount importance in addition to excellent gradient-amplitude stability and waveform reproducibility.
Further background techniques, which could be relevant for magnetic resonance spectroscopic (MRS) imaging, are discussed in the following. For simplicity, the discussion is initially restricted to the mapping of one spectral and two spatial dimensions. In particular, a slice-selective excitation scheme to select a plane of thickness Δz at position z0 from the object under investigation is considered. As signal acquisition occurs in the time domain, data is collected in k-space (i.e. a reciprocal spatial-spectral space) with axes kx, ky, and kω (note that kω=t, where t is time). A subsequent Fourier transform permits reconstruction of an image with spatial dimensions x and y and chemical shift dimension ω. The same principles as described below may then be used to expand the EPSI variants in order to achieve encoding of three spatial plus one spectral dimension.
With hybrid EPSI techniques, only one-dimensional (1D) spatial information is encoded along with the spectral dimension in a single pass (“shot”) of the sequence. In particular, spatial-spectral encoding can be achieved by periodically inverting a trapezoidal read-out gradient of amplitude Gx to traverse k-space along a zig-zag trajectory while collecting a series of Ny gradient echoes [6]. Each gradient lobe encodes the same spatial information (i.e. evolution along the kx-axis) whereas the signal evolution from gradient echo to gradient echo encodes the spectroscopic information (i.e. evolution along the t-axis). Ideally, the interval between adjacent gradient echoes, Δtx/2 (i.e. one half of the modulation period), corresponds to the inverse of the spectral bandwidth in the reconstructed spectra (i.e. Δν=1/τω=2/Δtx).
For the remaining spatial dimension, a standard phase-encoding scheme preceding the echo-planar readout may be used [6-9], which has also been referred to as phase-encoded echo planar (PEEP). Alternatively, the direction of the read-out gradient may be rotated by an angle increment Δφ in the xy-plane in successive shots to obtain a projection-reconstruction echo-planar (PREP) hybrid technique [5, 10, 11]. As yet another alternative, the line-scan imaging approach may be combined with EPSI (also referred to as line scan echo planar spectroscopic imaging, LSEPSI) to avoid saturation problems when selecting a short TR [1, 12]. Besides periodically alternating trapezoidal gradients, other wave-forms including sinusoidal [9] and triangular modulations [13] have also been proposed for EPSI. An approach to halve the number of phase-encoding steps and thereby the overall scan time in PEEP variants involves adding small gradient blips (along the y-direction) in between even and odd read-out gradient lobes. The alternating blipped gradient may be applied during each reversal of the read-out gradient [14] or between pairs of even/odd read-out gradient lobes [15].
Apart from applying a simple excitation pulse of flip angle α or a spin-echo or stimulated-echo pulse sequence to excite spins in a slice (with subsequent 2D-spatial and spectral encoding) or in a 3D object (with subsequent 3D-spatial plus spectral encoding), it may be advantageous—especially in 1H spectroscopic imaging in vivo—to pre-localize a volume of interest (VOI) by combining a standard single-voxel technique, such as point-resolved spectroscopy (PRESS) [16] or stimulated-echo acquisition mode (STEAM) [17], and a spatial suppression sequence to selectively saturate the spin system outside the VOI (outer-volume suppression, OVS). In particular, such pre-localization and OVS schemes have been integrated along with water suppression (WS) in a modular fashion into an EPSI readout in the so-called proton echo-planar spectroscopic-imaging (PEPSI) technique [18].
Due to the periodic inversion of the read-out gradient scheme in all of the above EPSI variants, magnetic field inhomogeneities, imperfections in the gradient pulses, or eddy currents induced by gradient switching lead to periodic mismatches between odd- and even-numbered echoes and produce aliasing artifacts. An approach to eliminate aliasing is obtained by rearranging the echoes acquired with positive and negative gradient polarities to obtain two sets of echoes for separate reconstruction [5, 7, 9]. After correction for the sign inversion, both data sets are added to maintain the signal-to-noise ratio (SNR). A disadvantage of this strategy is a doubling of the dwell time (i.e. τω=Δtx) and, hence, a reduction of the spectral bandwidth by a factor of ½ (i.e. Δν=1/Δtx). This might lead to undersampling of high-frequency components and thus aliasing of resonances outside of the bandwidth into the observed spectral window, especially at high magnetic fields.
A method for retaining the spectral bandwidth is spatial-spectral oversampling, which also reduces chemical-shift artifacts but leads to a greater demand on the gradient performance [19, 20]. Other approaches to expand the spectral bandwidth include shifting of the gradient modulation sequence with respect to the excitation pulse by a variable delay, tD, in subsequent shots [21] or increasing the amplitudes of the negative gradient lobes to concomitantly reduce their duration [7, 9]. A disadvantage of shifting the gradient modulation sequence is an increased scan time by a factor corresponding to the number of different delays. Shorter modulation periods achieved by asymmetric gradient modulation come at the expense of an SNR loss because only echoes refocused during the positive lobes can be used for image reconstruction. The bandwidth may also be preserved by appropriately splicing together the signals for subsequent experiments with cyclically inverted starting phases of the gradient waveforms, which requires two permutations (i.e. a two-shot experiment) in the case of 1D spatial encoding [5].
In principle, continuous data sampling during the entire gradient waveform is advantageous to minimize the acquisition bandwidth and thus improve the SNR [22]. This implies that even with trapezoidal gradients nonlinear sampling is used during some fraction (i.e. the ramp times) of the total acquisition window. This requires appropriate interpolation (regridding) of the data to correct for ramp-sampling distortions of the k-space trajectory. In addition, chemical-shift artifacts become a function of k-space encoding during ramp sampling, which may cause edges of chemically shifted species, such as peripheral lipid signals, to be more displaced than metabolite resonances.
Single-shot encoding of two spatial dimensions along with the spectral dimension is theoretically possible if two gradients, Gx and Gy, are periodically inverted. With echo-planar shift mapping (EPSM), both gradients are modulated in a trapezoidal fashion but with different amplitudes and modulation periods (e.g. Gy<Gx and 2Δty>2Δtx) [5, 23]. It is noted the technique of splicing together signals from subsequent experiments with cyclically inverted starting phases of the gradient waveforms to correct for aliasing under preservation of the spectral bandwidth as described above requires four permutations (i.e. a four-shot experiment) in the case of 2D spatial encoding [5]. A major problem with using a relatively long flat-top time of a trapezoidal gradient (i.e. a constant gradient) for phase encoding is that the samples are not uniformly spaced on a rectilinear k-space grid, which requires regridding of the data prior to the Fourier transform.
More recently, a single-shot variant of the PEPSI technique has been proposed that utilizes parallel-imaging techniques for obtaining 2D spatial encoding during a single spectral dwell time [24, 25].